Aryl amino compounds



Patented Oct. 1, 1940 UNITED STATES ARYL AMINO coMro- NDs Frederick F.Blicke, Washtenaw County, Mich, assignor to The Regents of TheUniversity of Michigan, Ann Arbor, Mich, a body corporate of Michigan NoDrawing.

Application March 6, 1939,

Serial No. 260,175

23 Claims.

The invention relates to the preparation of aminoalkyl esters ofnaphthalene carboxylic acids having an amino group attached to thenaphthalene nucleus.

The general formula for the compounds of the invention is,

where R is an alkyl residue (having either a straight or branched carbonchain), and R, R", R and R'v are the same or different members of thegroup hydrogen and an alkyl group (either straight or branched carbonchain).

This application is a continuation-in-part of my copending application,Serial No. 186,732, filed January 24, 1938.

The compounds of the invention are valuable for their physiologicalproperties, especially their anesthetic properties. They may also serveas intermediates for the preparation of other pharmaceutically valuablecompositions.

The new compounds can be made by various methods. For example,ahitro-haphthOic acid is converted into its acid halide,

c OHal and the latter compound reacted with an amino alkanol,

This nitro ester is then reduced at its nitro group to an amino compoundof the new type.

In order to obtain compounds where the amino group attached to thenaphthalene nucleus is substituted by one or more alkyl groups, and alsowhere unsubstituted, other more convenient methods can be used. Forexample, a naphthoic acid substituted in the nucleus by an amino-, a

monoalkylamino, or dialkylamino-group can be esterified by any of theusual methods in order to replace the hydrogen of the carboxylic acidgroup with an aminoalkyl radical, obtained for instance from anamino-substituted alcohol. In such cases, the amino naphthoic acid canbe esterified with an amino alcohol, or the alkali salt of the aminonaphthoic acid may be reacted with the corresponding amino-substitutedalkyl halide.

One may also replace the acidic hydrogen atom of an amino naphthoicacid, carrying a nuclear unsubstituted amino group, by an aminoalkylradical, using any of the known esterification reactions, and, ifdesired, subsequently treat the amino naphthoic acid ester with an alkylhalide or other alkylating agent to replace one or more of the aminohydrogen atoms by an alkyl group.

Instead of esterifying the naphthoic acid compound with an aminoalkylalcohol, it is possible to first esterify with an alcohol not containingan amino group, such as ethanol, and then treat the resulting ester withan amino alcohol in presence of a catalyst, such as sodium ethylate, tosplit 01? an alcohol from the ester and convert the alkyl ester into anaminoalkyl ester of an amino-substituted naphthoic acid.

The new compounds can be obtained in the form of their free amino basecompounds or in the form of their salts with organic and inorganicacids, such as hydrochloric, hydrobromic, nitric, citric, tartaric,sulfuric, phosphoric and other acids. In the salts, the acid group HX(where X is an anion radical of an organic or inorganic acid), isattached to an amino nitrogen atom. The free base compounds can be re- 5covered from their salts by treatment with basic or alkaline reagents.In those instances where one starts with the free base compound, saltscan be produced either by partial or complete neutralization of the freebase with a suitable acid.

The invention can be illustrated by the following examples:

EXAMPLE l.3-nitro-1-naphthoyl chloride EXAMPLE 2.-Hyclrochloride ofbeta-diethylaminoethyl ester of 3-m'tro-1 maphthoic acid To 24.0 gramsof 3-nitro-1-naphthoyl chloride, suspended in 130 cc. of dry benzene,there are added 12.0 grams of beta-diethylaminoethanol. The mixture isheated for two hours on a steam bath, the semi-solid mass cooled and thebenzene removed by filtration with suction. The dry hydrochloride of theester is dissolved in 100 cc. of water (if necessary the mixture iswarmed slightly), filtered, and the basic ester precipitated by theaddition of sodium carbonate solution. The oily product is extracted"with ether, the ether solution dried with fused sodium sulfate and thentreated with a stream of dry halogen chloride. The solid, practicallycolorless precipitate of the hydrochloride is recrystallized fromalcohol; Ml 211-213"; yield, practically quantitative.

Anal. calc. for C17H21O4N2Cl: Cl, 10.06. Found: Cl, 10.04.

EXAMPLE 3.Mono-hydrochloride of beta-diethylaminoethyl ester of3-amino-1-naphthoic acid Twenty-eight grams of stannous chloride(S11C12.2H2O) are added to 14.0 grams of ,the hydrochloride ofbeta-diethylamino ester of 3- .nitro-l-naphthoic acid, dissolved orsuspended 'in cc. of acetic acid and the mixture treated with a rapidstream of dry hydrogen chloride. The stannous chloride soon dissolvesand the tin addition product of the hydrochloride of the amino compoundsoon precipitates in crystalline form. During the reduction process themixture is cooled frequently in order that the temperature of themixture does not exceed 40 C. The material is filtered on a Jena filter,washed with a small amount of acetic acid, dissolved in the smallestpossible amount of water, the solution filtered, cooled with ice andtreated with 10% sodium hydroxide solution. The oily base isextractedwith ether, the ether solution dried with fused sodium sulfate,poured into a weighed. evaporating dish and the ether removed. Thecalculated amount of concentrated hydrochloric acid necessary for theformation of a monohydrochloride is added to the oil and the mixturestirred. The product crystallizes rapidly; yield, 10 grams. The salt isrecrystallized from alcohol and then washed with ether; M.P. 148-150".

Anal. calc. for C1'1H23O2N2C12 Cl, 10.99. Found: C1, 10.94.

EXAMPLE 4.4-nitro-Z-naphthoyl chloride A mixture or" 54.2 grams of4-nitro-1- naphthoic acid (Lueck, Perkins and Whitmore, J. Am. Chem.Soc. 51, 1831 (1929), and 52.0 grams of phosphorous pentachloride isheated on a steam bath for 45 minutes. The phosphorus oxychloride is rmoved under diminished pressure and the crystalline acid chloriderecrystallized from petroleum ether (90-100") or distilled under greatlyreduced pressure; yield, 54 grams; M.P. 96.

EXAMPLE 5.Hydrochlorideoj beta-diethylaminoethyl ester of4-nitro-1-naphthoic acid This compound is prepared in the same manner asthe corresponding 3-nitro derivative described in Example 2.

From 24 grams of the acid chloride there is obtained 26 grams of thehydrochloride of the ester; M.P.

EXAMPLE 6.Mono-hydrochloride of beta-diethylaminoethyl ester of4-amino-1-naphthoic acid A mixture of 17.6 grams of the hydrochloride ofthe beta-diethylaminoethyl ester of 4-nitro-1- naphthoic acid, suspendedin 30 cc. of acetic acid, and 35.0 grams of stannous chloride is treatedwith hydrogen chloride. The material soon dissolves, but the tin doublesalt separates very slowly. After four or five days the precipitatedmaterial is filtered on a Jena filter, washed with acetic, dissolved ina small amount of water, treated with charcoal and filtered. The oilybase is precipitated by the addition of 10% sodium hydroxide solution,extracted with ether, the ether solution dried with fused sodium sulfateand treated with hydrogen chloride. The crystalline precipitate ofdihydrochloride is washed with absolute alcohol and then with dry ether.It is dissolved in water, the base precipitated by the addition ofsodium carbonate solution, extracted with ether, the solution dried andthe solvent removed in a weighed evaporating dish. The crystallinemono-hydrochloride is obtained by the addition of the calculated amountof concentrated hydrochloric acid to the oily base. Themono-hydrochloride is recrystallized twice from water; M.P. 2l4216.

Anal. calc. for C1'7H23O2N2C11 Cl, 10.99. Found: Cl, 10.87.

The invention is not limited to the naphthoic acid derivatives used inthe above examples. For instance Z-naphthoic acid can be used and thefollowing derivatives can be obtained, some by direct, others byindirect, procedures: l-nitro-Z- naphthoic, 3-nitro-2-naphthoic,l-nitro-Z-naphthoic, S-nitro-Z-naphthoic, 6-nitro-2-naphthoic,Z-nitro-Z-naphthoic and 8--nitro-2-naphthoic acid. The correspondingnitroand amino-substituted derivatives are obtained when starting withthese acids and using the procedures mentioned above.

The following list gives some of the new compounds, with their meltingpoints:

Compounds 1 and 4 were recrystallized from alcohol, compound 2 fromdilute alcohol, and compounds 3 and 5 from benzene.

All of the compounds Were colorless except compound 4 which was lightbrown.

Mono hydrochlorides of esters of 3-amz'no-1- naphthoic acids RI 4 M. PNo. Ester Radical -R-N (degrees Formula 1. B-dicthylaminoethyl.CHHQSOQNQCI 2. fi-d1-n-butylaminoethyl CnHarOzNzCl 3.fl-di-n-butylaminopropyl. CzzH3302N2C1 4 a-d1ethylaminopropyl C1gH2OzNzCl 5 a-di-n-butylaminopropyl CzzHsaOzNzCl Compound 1 wasrecrystallized from alcohol;

all of the other compounds were recrystallized from a mixture of ethylacetate and acetic acid.

Hydrochlorides of esters of 4-nitro-1-naphthoic Compound 1 wasrecrystallized from ethyl alcohol, compound 3 from ethyl acetate,compound 5 from absolute alcohol and compound 6 from benzene.

Mono hydrochlorides of esters of 4-amino- 1- naphthoic acids R! M. P No.Ester radical --R-N (degrees Formula 1 fl-diethylaminoethyl.- 214-216onnaolNzm fl-din-butylaminoethyL- 170-171 Cz1Ha1O2N2 1 3-.-..B-diethylaminopropyl--- CuHetOzNzCl 4. fl-di-n-butylaminoprop lC22H33OzN2 5..- a-diethylaminopropyl. C18H25O2N201 6-...-wdi-n-butylaminopropyl C22H33O2N2Cl Compounds 1 and 3 wererecrystallized from water, compound 2 from alcohol, compound fromabsolute alcohol and compounds 4 and 6 from a mixture of ethyl acetateand acetic acid. The sulfamate correspondingto compound 1 having theformula, C17H2505N3S, melts at 139- Compound 1 was recrystallized fromabsolute alcohol, compound 2 from water and then from benzene, compound3 from ethyl alcohol, compound 4 from butyl alcohol and compound 5 fromethyl acetate.

Mono hydrochlorides of esters of S-amino-Z- naphthoi c acids" RI. H M.No Ester radical -R-N .(degrecs Formula fl-diethylaminoethyl--.CuHzsOzNzCl B-di-n-butylaminoethyl. O2lH3lO2N2G1 B-diethylaminopropylC18H2502N2C1 a-diethylaminopropyl 175-177 CIBHE502N201a-di-n-butylaminopropyl 159-160 O22H3302N1C1 Compound 1 wasrecrystallized from alcohol. The sulfamate corresponding to compound 2and having the formula, C21H33O5N3S, melts at 118- The compounds listedabove were prepared by procedures analogous to those given for thecorresponding compounds of Examples 1 to 6. In everyinstance, analysisof the compounds gave a percentage of chlorine almost exactly thatrequired by theory for the empirical formula given for eachhydrochloride.

The invention in its broader features includes preparation of aminoalkyl esters of amino naphthoic acids wherein the carboxylic acid group,orits corresponding ester group, and the nuclear amino group areattached in any of the available relative positions around the twocarbon rings of the naphthalene nucleus. For instance, the 6-amino-,l-aminoand 8-aminoderivatives corresponding to the above listed 3-amino-, -4-amincand 5-amino-derivatives of 1- naphtho ic acid can alsobe made in the same manner. An example of a G-amino-derivative is asfollows:

EXAMPLE '7.Preparati0n of the beta-diethylaminoethyl ester of6-amz'no-1-naphthozc acid and its intermediate nitro compound .4.6-nitro-1-ataphth0yl chZoride.A mixture of 20 grams ofG-nitro-l-naphthoic acid and 44 grams of thionyl chloride, purifiedaccording to the method of Fieser (Fieser, Experiments in OrganicChemistry, D. C. Heath, 1935, p. 339), is refluxed for six hours on anoil bath at 150. At no time does the solution become homogeneous, thegreater part of the acid chloride remaining insoluble in the thionylchloride. The excess thionyl chloride is then removed on the steam bathand the product used without further purification. A small portion isrecrystallized fro-mbenzene; M. P. 154-155. The 6- nitro-l-naphthoicacid used in this preparation is obtained by the method of Leuck,Perkins and Whitmore (J. Chem. 800., 51, 1831, 1929).

Calcd. for CnHeOsNClZ 01, 15.07. Found: Cl, 14.82.

B. Hydrochloride of p-diethylaminoethyl ester of 6-mtro- 1-naphthoicacid-To the crude acid chloride described above, dissolved in 85 cc. ofdry, benzene, therejis added 20 grams of diethylaminoethanol. Themixture is refluxed two hours on the steam bath, during which time theester separates as a very dark solid. After standing fifteen hours atroom temperature, the product is filtered oil and washed with petroleumether (30-60). It is then treated with a 10% sodium carbonate solutionand the free base extracted with ether and dried over fused sodiumsulphate. The hydrochloride is precipitated with a stream of hydrogenchloride gas and recrystallized from absolute alcohol; P.

Calcd. for C1'1H210'4N2C1I 01, 10.06. Found: Cl, 10.08. C.Monohydrochloride of B-tiietfiyluminoethyl ester "offi-amino-i-naphthoic acid.-To 1.2 grams of the product obtained above,dissolved in 5 cc. of glacial acetic acid, there is added 2.4 grams ofstannous chloride dihydrate. An excess of hydrogen chloride gas ispassed in, keeping the mixture cooled below 45". After standing sixteenhours, the mixture is made alkaline with 10% sodium hydroxide solutionand the'free base, an oi1,taken up in ether and dried over fused sodiumsulphate. The ether is then removed, and to the base is added thecalculated amount of concentrated hydrochloric acid to make themonohydrochloride. The product crystallizes from absolute alcohol aslight tan needles; M. P. 169-170.

Calcd. for CrzHzsOzNzClI Cl, 10.99. 11.08.

In addition to the above compounds, the following examples ofpreparation of branchedchain alkyl derivatives are given:

EXAMPLE 8.-Hydrochloride of ,cfi-dimethyl-vdimethylaminopropyl ester of4-nitro-1-naphthoic acid Found: Cl,

of the ester is obtained by diluting the mother liquor with petroleumether (30-60). The pale yellow product is recrystallized from a mixtureof ethyl acetate and glacial acetic acid; M. P. 150451"; yield 14.5 g,or 78% of the calculated amount.

Calculated for C1BH2304N2C1; Cl, 9.67. Found: Cl, 9.86.

EXAMPLE 9.Mon0hydrochloride of cfi-dimethyl- -d-imethylaminopropyl esterof 4-amz'no-1- naphthoic acid To 7.34 g. of the product obtained inExample 8, dissolved in 12 cc. of glacial acetic acid, there is added 14g. of stannous chloride dihydrate. The mixture is cooled rapidly inorder that the temperature be maintained below 45. The clear solution istreated with a rapid stream of dry hydrogen chloride gas and the mixturecooled at intervals until no further heat of reaction is liberated.After standing two hours, the solution is made alkaline with sodiumhydroxide solution, and the free base, an oil, taken upin ether anddried over fused sodium sulphate. The ether is then removed, and to thebase there is added the calculated amount of concentrated hydrochloricacid to make the monohydrochloride. The pale yellow product isrecrystallized from alcohol; M. P. about 221 C.

lized from a mixture of ethyl acetate and glacial acetic acid; M. P.151-152"; yield 16 g., or 80% of the calculated amount.

Calculated for C2oH2 7O4N2C1; Cl, 8.98. Found: Cl, 9.07.

EXAMPLE 11.-Monohydrochloride of cfl-dimethyl-y-diethyldminopropyl esterof 4-amino-1- naphthoic acid To 7 .9 g. of the product obtained inExample 10, dissolved in 12 cc. of glacial acetic acid, there is added14 g. of stannous chloride dihydrate. The product is then reduced withhydrogen chloride gas being passed into the solution and worked up inthe same manner as the product of Example 9. The monohydrochloridecrystallizes from alcohol as yellow needles; M. P. 184-186.

Calculated for CH29O2N2C1; Cl, 9.72. Found: Cl, 9.59.

EXAMPLE 12.Hydrochloride of dc-di'methyldimethylaminopropyl ester of3-nitro-1-naphthoic acid This compound is prepared in the same manner asthe corresponding 4-nitro ester of Example 10. The colorless productcrystallizes from absolute alcohol in the form of needles; M. P.203-204". A small amount of material, isolated from the mother liquid byevaporation and treatment with petroleum ether, can be identified as thefree base. It crystallizes from absolute alcohol in the form of yellowcubes; M. P. 114-115".

Calcd. for C1BH2304N2C1Z Cl, 9.67. Found: Cl, 9.71.

EXAMPLE 13.Monohydrochloride of Bfi-dimethyl- -dimethylaminopropyl esterof 3-amino- Imaphthroic acid This compound is prepared from the nitroester of Example 12 in the same manner as the 4-amino analog of Example11. The monohydrochloride is recrystallized from n-butanol and has theform of orange needles; M. P. 162-163.

Calcd. for C1BH25O2N2C1Z Cl, 10.53. Found: Cl, 10.44.

Some of the nitro-naphthoyl halide intermediate compounds which can beused in this invention are new compounds. For example, the followingcompounds have been made:

Nitronaphthoyl chlorides No. Chloride M. P., C. B. P., 0. Formula Calcd.Found 1 B-nitro-l-naphthoyl 137-139 205-206/12 mmuu'. CuHsOaNC-l 15. 0715.05 2 4-n tro-l-uaphthoyl 96 208-210/17 Inm C H6O3NCL 15.07 14. 90 3fi-n tro-l-naphthoyl 132-134 214-217/18 mm. OllHfiOfiNCl. 15.07 14.96 46-nitr01-naphthoyl 154-155 CHHGOKNGI 15.07 14. 82

Calculated for Found: Cl, 10.51.

EXAMPLE 10.-Hydrochloride of pfi-dimethyl diethylaminopropyZ ester of4-nitro-1-naphthoic acid To 12 g. of 4-nitro-1-naphthoyl chloridedissolved in 65 cc. of dry benzene, there is added 8 g. of e,p-dimethyl--diethylaminopropanol. The amino alcohol is prepared according to theunmodified procedure of Mannich (Ber. 65, 378 (1932)). The mixture isrefluxed four hours on the steam bath, during which time the esterseparates as an oil. On cooling and Washing with petroleum ether(SO-60), the oil becomes crystalline. The colorless product isrecrystal- CisI-IzsOzNzCl; Cl 10.53.

Compounds 1 and 4 were recrystallized from benzene, compounds 2 and 3from petroleum ether (90-100).

Method of preparation of the above nitronaphthoyl-chlorides of the type,

ride was used. Solid material was present in the reaction flask duringthe whole procedure and no complete solution was obtained.

In the final compounds, the amino group attached to the naphthalenenucleus may be attached either to the same carbocyclic ring as that towhich the carboxyl group is attached or may be attached to the otherring of the naphthalene nucleus. For instance, instead of starting inExample 1 with 3-nitro-1-naphthoic acid, one can also use thecorresponding .Z-nitro, 4-nitro, 5-nitr0, 6-nitro, '7-nitro or 8-nitroderivatives of l-naphthoic acid, or even the corresponding nitroderivatives of an isomeric naphthoic acid, where the carboxyl groupoccupies one of the positions in the naphthalene nucleus other thanposition 1.

In forming esters of the amino-naphthoic acids or their correspondingnitro intermediates, it is not necessary to use p-diethylamino ethanolas the alcohol for reaction with the substituted naphthoic acid halide.Any other alcohol, aminoalkyl alcoho l, or alkylamino alkyl alcohol maybe reacted with a nitroor aminonaphthoic acid .halide or equivalentcarboxylic acid derivative capable of reacting with the alcohol to givethe corresponding carboxylic acid ester. By choosing a suitableaminoallgyl alcohol, the number of methylene groups between thecarboxylic acid and the amino group at the other end of the al- .kylenechain can be given any number desired.

but where R isan aliphatic hydrocarbon residue, straight or branchedchain, containing not more than four carbon atoms in the chain, and R,R, R a'nd Riv are the same or different members of the group hydrogenand an alkyl than four [carbon atoms. Compounds in this sub-group are ofoutstanding value for their physiological properties, especially theirlocal anestheticproperties. For instance, compounds f HiN- where the Rgroups have the significance lastgiven above, such as the product ofExample 6, are more active anesthetics for topical application thanprocaine and in many cases they are more active than cocaine. In spiteof their high anesthetic activities, they are of surprisingly lowtoxicity.

Under this formula, which is for compounds having a nuclearunsubstituted amino group, is a class of compounds which includes manyof the more effective anesthetics and which may be represented by theformula,

where R is an alkyl residue and R and R" are alkyl groups, R,'R.' and'R"each containing not more than 4 carbon atoms. In these compounds theunsubstituted amino group (-NHz) is attached to the same; G-memberedcarbocyclic nucleus as the carboxylic acid group and is also attached tothe No. 3*or No. 4 carbon atoms. These are the only available carbonatoms of said nucleus not adjacent to the-carbon atom to which thecarboxylic acid group is attached.

A few examples of compounds which can be made in accordance with theinvention are, the p-diethylaminoethyl esters of 2-amino-, 5-amino-,6-amino-, '7-amino-, and 8-amino-l-naphthoic acids and the e-dibutylaminoethyl esters of these same amino naphthoic acids, as well as their-diethyl aminopropyland -dibutyl aminopropylesters. Other examples arethe corresponding esters of amino naphthoic acids with the carboxylicacid group in position 2 in the naphthalene ring.

The invention not only includes new anesthetic products but alsoprovides new chemical substances, especially in their substantiallychemically pure crystalline forms capable of practical therapeutic use.

The anesthetic substances of this invention can be used either alone orin combinations with other therapeutically useful substances, such forexample as vaso-constrictors like adrenalin or epinephrine, with orwithout buffer salts and other ingredients. 1

Compounds coming within the purview of the invention are the free aminobase compounds and their salts with various organic and inorganic acids,such as citric, tartaric, sulfuric,

sulfamic (I-IO'-SO2NH2), other acids. There are two amino groups presentin each of the final compounds and the invention includesnot onlythemono-salts of the lactic, boric and free amine bases, containing oneequivalent of acid to one of the base, but also the salts wherein twoequivalents of acid are combined with one of the amine. For example, allof the monohydrochlorides of the amino naphthoic acids listed above canbe prepared in the form of their di-hydrochlorides by using asecond-equivalent of hydrochloric acid. V

What I claim as my invention is:

1. Aminoalkyl esters of amino-naphthalene carboxylic acids and theiracid addition salts represented by the following formula for the esters,

where R is an alkylene group containing not more,

than 4 carbon atoms and R, R", R' and R'o are members of the grouphydrogen and an alkyl radical containing not more than 4 carbon atoms.

3.Aminoalky1 esters of amino-naphthalene carboxylic acids and their acidaddition salts represented by the following formula for the esters,

RI COORN where R is a lower alkylene group and R and R."

are members of the group hydrogen and an alkyl radical containing notmore than 4 carbon atoms.

' 4. Aminoalkyl esters of amino-naphthalene-lcarboXylic acids and theiracid addition salts represented by the following formula for the esters,

where R is an alkylene group of not more than 4 carbon atoms and R andR" are members of the group hydrogen and an alkyl radical containing notmore than 4 carbon atoms.

5. A salt of an aminoalkyl ester of aminonaphthalene-l-carboxylic acidrepresented by the following formula,

Where R is an alkylene group of not more than 4 carbon atoms and R andR." are members of the group hydrogen and an alkyl radical containingnot more than 4 carbon atoms.

7. Gamma-di-n-butylarninopropyl esters of amino-naphthalene-l-carboxylicacids and their acid addition salts represented by the following formulafor the esters,

8. The beta-di-ethylaminoethyl ester of 4-ami- -no-l-carboxylic acid andits acid addition salts represented by the following formula for theester,

COOCH2CHz-N 9. As new anesthetics, the mono-hydrochlorides ofamino-napthalene-l-carboxylic acid aminoalkyl esters represented by thefollowing formula,

Where R is an alkylene group of not more than 4 carbon atoms and R andR" are members of the group hydrogen and an alkyl radical containing notmore than 4 carbon atoms, n being a whole number not greater than 2.

10. As an anesthetic substance, the mono-hydrochloride of thebeta-diethylaminoethyl ester of 4-amino-1-naphthoic acid.

11. As an anesthetic substance, the mono-hydrochloride of thegamma-di-n-butylaminopropyl ester of 3-amino-1-naphthoic acid.

12. As an anesthetic substance, the mono-hydrochloride of thegamma-di-n-butylaminopropyl ester of 4-amino-1-naphthoic acid.

13. Process for the preparation of an aminoalkyl ester of anamino-naphthalene carboxylic acid which comprises reacting the acidhalide of a nitro-naphthoic acid with an amino-alkanol to form anitro-naphthoic ester and reducing the nitro group of the latter to anamino group.

14. Process for the preparation of a dialkyl aminoalkyl ester of anamino-substituted 1- naphthoic acid which comprises reacting an acidhalide of a nitro-substituted l-naphthoic acid with a dialkylaminoalkanol to form a nitronaphthoic ester and reducing the nitro groupof the latter to an amino group.

15. Process for the preparation of the gammadi-n-butylaminopropyl esterof 3-amino-1- naphthoic acid which comprises reacting 3-nitrol-naphthoicacid halide with gamma-di-n-butylaminopropanol to form thegamma-di-n-butylaminopropyl ester of 3-nitro-1-naphthoic acid andreducing the nitro group of the latter to an amino group.

16. An acid addition salt of an aminoalkyl ester of amino-naphthalenecarboxylic acid represented by the following formula for the ester whereR is a lower alkylene group and R, R, R and R are members of the grouphydrogen and an alkyl radial containing not more than 4 carbon atoms.

17. An acid addition salt of the beta-diethylaminoethyl ester of4-amino-1-naphthoic acid.

18. An acid addition salt of the gamma-di-nbutylaminopropyl ester of3-amino-1-naphthoic acid.

19. An acid addition salt of the gamma-di-nbutylaminopropyl ester of4-amino-1-naphthoic acid.

20. Process for the preparation of an aminoalkyl ester of anamino-naphthalene carboxylic acid which comprises converting anitro-naphthoic acid into its acid halide with a halogenating agent,reacting the acid halide with an aminoalkanol to form a nitro-naphthoicacid ester, reducing the nitro group of the latter to an amino groupwith production of an aminoalkyl ester of an amino-naphthalenecarboxylic acid and adding a quantity of acid to form an acid additionsalt with the latter ester.

21. Process for the preparation of a dialkyl aminoalkyl ester of anamino-substituted-lnaphthoic acid which comprises converting anitro-substituted-l-naphthoic acid into its acid halide with ahalogenating agent, reacting the acid halide with a dialkyl aminoalkanolto form a nitro-naphthoic acid ester, reducing the nitro group of thelatter to an amino group with production of the dialkyl aminoalkyl esterof an amino-substituted-l-naphthoic acid and adding a quantity of acidto form an acid addition salt with the latter ester.

22. Process for the preparation of the betadiethylaminoethyl ester of4-amino-1-naphthoic acid which comprises converting -nitro-l-naphthoicacid into its acid halide with a halogenating agent, reacting the acidhalide with beta-diethylaminoethyl ethanol to form abeta-diethylaminoethyl ester of 4-nitro-1-naphthoic acid, reducing thenitro group of the latter to an amino group with production of abeta-diethylaminoethyl ester of 4-amino-1-naphthoic acid and adding aquantity of acid to form an acid addition salt with the latter ester.

23. Process for the preparation of an acid addition salt ofgamma-di-n-butylaminopropyl ester of 3-amino-1-naphthoic acid whichcomprises converting 3-nitro-1-naphthoic acid into its acid halide witha halogenating agent, reacting said acid halide withgamma-di-n-butylaminopropanol to form the gamma-di-n-butylaminopropylester of 3-nitro-1-naphthoic acid, reducing the nitro group of thelatter to an amino group and adding a quantity of acid to form an acidaddition salt with the latter ester.

FREDERICK F. BLICKE.

